Outline

Introduction: The aim of this study is to determine the effect of statins alone and in combination with microcapsulotomy on renal ischemia-reperfusion (I/R) injury. As chronic inflammatory reactions predispose to fibrosis and dysfunction, the impact on macrophages as the characteristic cell type in chronic inflammation is of particular interest.

Material and methods: I/R injury was induced by 45 min clamping of kidney vessels of Balb/C nu/nu mice. Renal function was measured using 99mTc-MAG3 scintigraphy. Renal injury was determined by a renal injury score. The inflammatory infiltrate was analyzed by immunohistochemistry for F4/80, a marker of mature macrophages. Controls were compared to a simvastatin monotherapy and a combination therapy of simvastatin and microcapsulotomy.

Results: I/R injury led to a marked reduction in renal function. Renal clearance was reduced by more than 80% as compared to baseline (day 2: 19.1%Â±3.8%, p<0.05 vs. baseline; day 18: 19.9%Â±9.2%, p<0.05 vs. baseline). Controls developed massive tissue damage and exhibited a 17-fold higher infiltration of F4/80 labeled macrophages compared to healthy kidneys. Simvastatin as well as microcapsulotomy for its own had no significant effect on I/R injury. However, the combination of both therapies showed a significant improvement of renal clearance (day 2: 51.5%Â±12.5%, p<0.05 vs. baseline; day 18: 87.1%Â±9.1%, n.s. vs. baseline), decreased tissue damage, and a reduction of macrophage infiltration (1.8-fold compared to healthy kidneys).

Conclusion: Combination of simvastatin and microcapsulotomy improves renal function, reduces macrophage infiltration, and preserves structural integrity after renal I/R. Microcapsulotomy may create a permissive environment for the beneficence of statins.